Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming, and long non-coding RNAs.
Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming, and long non-coding RNAs.
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转座元件位于胚胎发生、胚胎干细胞、重编程和长非编码RNA之间十字路口的中心
DOI：
10.1007/s11434-015-0905-x
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发表时间：
2015
期刊：
影响因子：
18.9
通讯作者：
Pei D
中科院分区：
文献类型：
--
作者：
Hutchins AP;Pei D
转座元件 (TE) 是能够自主和非自主复制的 DNA 移动基因组序列。 TE 非常成功，现在近一半的人类基因组由不同的 TE 家族组成。这些元件最初被认为是非功能性的，但已被动物基因组选择来执行各种生理功能，从直接作用于正常生物功能的 TE 衍生蛋白，到转录因子逻辑的创新以及对基因表达的表观遗传控制的影响。在胚胎发育过程中，当基因组进行表观遗传重编程和DNA去甲基化时，TE从抑制中释放并显示出胚胎阶段特异性表达，在人类和小鼠胚胎中，甚至可以检测到完整的TE衍生的内源病毒颗粒。类似的过程发生在体细胞重编程为多能细胞的过程中：当体细胞DNA去甲基化时，TE从抑制中释放出来。在 DNA 低甲基化的胚胎干细胞 (ESC) 中，采用复杂的表观遗传控制系统来抑制 TE，该系统通常与 ESC 基因表达的正常表观遗传控制重叠。最后，许多参与正常 ESC 功能的长非编码 RNA (lncRNA) 以及那些协助或损害重编程的 RNA 中含有多个 TE。这些 TE 可以作为调节单元来招募 RNA 结合蛋白和表观遗传修饰剂。这篇综述涵盖了 TE 如何与表观遗传机制和 lncRNA 相互联系，以及这些联系如何相互影响以调节 ESC、胚胎发生和体细胞重编程的各个方面。
Transposable elements (TEs) are mobile genomic sequences of DNA capable of autonomous and non-autonomous duplication. TEs have been highly successful, and nearly half of the human genome now consists of various families of TEs. Originally thought to be non-functional, these elements have been co-opted by animal genomes to perform a variety of physiological functions ranging from TE-derived proteins acting directly in normal biological functions, to innovations in transcription factor logic and influence on epigenetic control of gene expression. During embryonic development, when the genome is epigenetically reprogrammed and DNA-demethylated, TEs are released from repression and show embryonic stage-specific expression, and in human and mouse embryos, intact TE-derived endogenous viral particles can even be detected. A similar process occurs during the reprogramming of somatic cells to pluripotent cells: When the somatic DNA is demethylated, TEs are released from repression. In embryonic stem cells (ESCs), where DNA is hypomethylated, an elaborate system of epigenetic control is employed to suppress TEs, a system that often overlaps with normal epigenetic control of ESC gene expression. Finally, many long non-coding RNAs (lncRNAs) involved in normal ESC function and those assisting or impairing reprogramming contain multiple TEs in their RNA. These TEs may act as regulatory units to recruit RNA-binding proteins and epigenetic modifiers. This review covers how TEs are interlinked with the epigenetic machinery and lncRNAs, and how these links influence each other to modulate aspects of ESCs, embryogenesis, and somatic cell reprogramming.